An orodispersible tablet is a solid form that disintegrates or dissolves in the mouth, solely on contact with saliva, generally in less than 60 seconds.
Orodispersible tablets are a galenical form that is on the rise, which has greatly developed in recent years. The reason for this is that orodispersible tablets have many advantages and are particularly suited to patients who have difficulties in swallowing, for example children and the elderly. However, these populations are not the only ones presenting with dysphagia, since about 30 to 50% of the population is concerned by this problem. Many adults are also concerned, and especially patients with psychiatric disorders, but also those suffering from thyroid complaints, Parkinson's disease, immune system deficiency diseases (AIDS), gastrointestinal reflux, and also patients suffering from nausea, vomiting or travel sickness. Orodispersible tablets are also suitable for people who do not have ready access to water, especially when travelling. Another advantage of said tablets is that they allow a practical and discreet use.
To allow rapid disintegration, orodispersible tablets have a porous structure and are compressed at lower pressures than conventional tablets, the drawbacks being that they may be more fragile and difficult to handle.
A large number of methods for obtaining orodispersible tablets have been developed in recent years.
However, there are still at the present time certain characteristics that limit the industrial development of orodispersible tablets, especially their excessive friability and their occasionally unpleasant taste and mouthfeel.
Thus, although orodispersible tablets remain a fairly widespread form that patients appreciate, especially for their practical and rapid use, a study performed by the Applicant has shown that the taste and mouthfeel of a tablet appear to be the most important parameters for patients, and thus the unpleasant taste and/or unpleasant mouthfeel are one of the major causes of non-compliance with medical treatments, and thus of their failure.
One of the aims of the invention is thus to obtain an orodispersible tablet that has a pleasant mouthfeel and/or a pleasant taste in the mouth.
More precisely, one of the aims of the invention is to obtain an orodispersible tablet that has a disintegration time in the mouth of less than 60 seconds, preferably less than 40 seconds and even more preferentially less than 30 seconds, which has satisfactory friability, while at the same time having a pleasant taste and mouthfeel.
In patent application WO 03/039520, the described orodispersible tablets are obtained via a “direct compression” method, the main steps of which are summarized in FIG. 1. However, this direct compression method is not always entirely satisfactory, especially in terms of the friability and the disintegration time of the tablets thus obtained.
The Applicant has now found, surprisingly, that orodispersible tablets with very satisfactory properties, as described above, could be obtained when they were prepared via a process known to those skilled in the art as compression molding.
Molding is a method in which the tablets are formed by compression of a wet powder, by solidification of a gel or by evaporation of a solvent. In the three cases, drying of the tablets or evaporation of the solvent takes place after forming the tablets. Three different molding methods exist: compression molding, heat molding and no-vacuum lyophilization.
Conventionally, the compression molding method is based on the compression of a wet mixture. This method comprises several steps: a powder mixture is moistened with an aqueous-alcohol solvent, and this wet mixture is then compressed at compression forces lower than those used in direct compression, which leads to a very porous structure. The large porosity of the tablets thus obtained allows very rapid disintegration (from 5 to 15 seconds). The tablets are then dried to remove the solvent therefrom.
The compression molding process usually uses soluble excipients (saccharides) which also contributes towards rapid disintegration and gives a pleasant taste and mouthfeel. The hardness may be very variable from one formulation to another. This is a difficult parameter to adjust, but it would appear that it is possible to obtain hardnesses higher than those obtained in direct compression.
In U.S. Pat. No. 5,501,861, a compression molding method was developed, in which a wet mixture of active principle, starches and sugars is compressed so as to obtain porous tablets, having a hardness sufficient for manufacture and a disintegration time of less than a minute. A similar method was also developed in U.S. Pat. No. 6,743,443.